Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

Effect of using vacutainers with cartoon characters on the pain and fear levels of preschoolers during bloodletting.

AIM: Our study aims to analyse the effect of using a vacutainer with cartoon characters on preschoolers' pain and fear levels during the bloodletting process. METHODS: The experimental, randomised controlled clinical trial was conducted with 102 children aged 3-6 years, randomised into control and experimental groups. The bloodletting routine was applied to the control group. The vacutainer of each child in the experimental group was covered with the illustration of their chosen cartoon character and blood was drawn with it. The fear and pain levels during the bloodletting procedure were examined in both groups. RESULTS: Pain and fear levels were significantly lower in the experimental group than in the experimental group (P < 0.05). CONCLUSIONS: Our research highlighted that using a cartoon character sticker with a vacutainer can reduce preschoolers' pain and fear during bloodletting.

How do I perform therapeutic phlebotomy?

BACKGROUND: Therapeutic phlebotomy (TP) is a well-established medical intervention that evolved from the historical practice of bloodletting. METHODS: Patients who require TP are not infrequently told by their health-care providers to "just go donate blood," but TP should always be offered in the context of a prescribed course of therapy. Providers can prescribe a course of TP for a number of indications, including hereditary hemochromatosis, polycythemia vera, iron overload, and testosterone replacement therapy. RESULTS: A course of prescribed TP specifies that patients can be phlebotomized more frequently than volunteer blood donors and reassures patients that TP is being performed per the orders of their provider. Prescribed TP also facilitates two-way communication between the referring provider and the transfusion medicine (TM) physician overseeing the TP. The College of American Pathologists TM checklist describes several requirements regarding the documentation and performance of TP, and electronic medical record systems can be used to demonstrate compliance with these requirements. CONCLUSIONS: TM physicians should discuss the advantages of prescribing TP with providers who mutually care for patients requiring this intervention.

Early Dental Trade Card for a Dentist & Cupper.

Very few "Dentist AND Cupper" trade cards are known and this is the only illustrated one known to the authors. "Mr. Glissan, Dentist and Cupper, 147 Blackfriars Road, (London), Teeth extracted for the Poor Gratuitously." Above the text and in the center is a eight-sided brass boxed scarificator. Developed in the 18th century as a more humane and efficient instrument for bloodletting than lancets or fleams, scarificators had multiple blades that shot out with the press of a spring-loaded lever creating an instantaneous series of parallel cuts in the skin of the patient. After the cuts were made a warm glass cup (to create a vacuum) was applied to drain blood. Two of these cups are pictured on each side of the scarificator. A mandible to the left and a maxilla to the right are also pictured. An explanation of the ancient procedure of cupping can be accessed at: https://www.webmd.com/balance/guide/cupping-therapy#1 (accessed 30 October 2020). Mr. Glessan's offer of free extractions for the poor is not unknown but seldom found on early dentist's trade cards.

Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies.

Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov .

Battle of the Bulge: Aortic Aneurysm Management From Early Modernity to the Present.

For centuries, physicians have recognized aortic aneurysms as an acute threat to life. Therapeutic approaches to the disease began in the 18th century when leading physicians, such as René Laennec and Antonio Valsalva, applied research on circulation and blood coagulation to devise whole-body fasting and bleeding regimens to prevent rupture. After John Hunter's success in ligating arteries to treat peripheral aneurysms, surgeons attempted analogous operations on the aorta, but even the renowned Sir Astley Cooper and William Halsted met with disastrous results. Other clinicians tried various methods of creating intraluminal clots, including the application of such new technologies as electricity and plastic. Vessel repair techniques, pioneered by Alexis Carrel and others in the 20th century, eventually provided a reliably effective treatment. In the past few decades, minimally invasive methods that approach aneurysms endovascularly through small groin incisions have been adopted. A successful 2005 congressional campaign to fund screening for aortic aneurysms brought the disease to national attention and symbolizes current confidence in curing it. Drawing on various published and unpublished sources, this paper elucidates the development of specific treatments for aortic aneurysms over time and more broadly addresses how medicine and surgery apply the knowledge and technology available in particular eras to treat a specific, identifiable, and lethal disease. Examining the evolution of these therapeutic efforts unveils broader trends in the history of medicine. This allows aortic aneurysms to serve as a case study for exploring shifting philosophies in medical history.

The Hippocratic Method of Surgical Cauterization for the Tumescence Spleen in the Rare "Spetses Syndrome".

Spleen in antiquity was considered by the Hippocratic medicine as a viscerous organ of spongy character, which could clear human body of the black bile. According to the Hippocratic doctrine of the 4 humors, black bile could cause a series of diseases. Both the anatomical position and shape of the spleen were also recognized. In the case of a splenic hardening, with simultaneous augmentation of its dimensions and dermal ulceration and/or splenic abscess, some interventions were proposed. Thus, herbal medicine, phlebotomy, and minimal surgery with local cauterization were applied for treatment, to confront a disease that was considered serious but not fatal. The Hippocratic physicians encountered various spleen diseases and among them they most probably confronted a rare splenic pathological entity, named centuries later as "Spetses syndrome," a rare type of thalassemia of the Spetses island of Saronikos Gulf. Although the approach seems in modern terms rather primitive, the ancient Greek medico-philosophers most likely understood the significance of the spleen.

[Coiling method combined with bloodletting from the corpus cavernosum for penile incarceration with a metal ring: A case report and literature review].

OBJECTIVE: To explore the treatment of penile incarceration with a metal ring. METHODS: Based on our experience in the successful management of a case of penile incarceration with a metal ring by coiling and bloodletting from the corpus cavernosum, we reviewed the relevant literature and analyzed the indications, advantages and disadvantages of different methods for the treatment of penile incarceration with a circular foreign body. RESULTS: The clamping and cutting methods were non-invasive, fast, effective, and with few complications, which could be applied to the treatment of penile strangulation at all levels. However, clamping was not desirable enough for a hard metal ring and the cutting method took a longer time and might increase the risk of unnecessary damage to the penile skin, urethra and cavernous body. Prepuce edema decompression and the thin tube-coiling method, with the advantages of minimal invasiveness, simple operation and no need of special tools, were suitable for penile strangulation injury under level 3, but might cause penile skin injury and potential postoperative erectile dysfunction. Surgical resection, as an invasive procedure, could be applied to severe penile strangulation at level 4 or 5. CONCLUSIONS: The principle for the treatment of penile incarceration with a circular foreign body is to remove the foreign object as soon as possible and not to add secondary damage.

The ameliorative effect of bloodletting puncture at hand twelve Jing-well points on cerebral edema induced by permanent middle cerebral ischemia via protecting the tight junctions of the blood-brain barrier.

BACKGROUND: Cerebral edema, erupting simultaneously with severe ischemic stroke, might lead to increased intracranial pressure, cerebral herniation, and ultimately death. Studies conducted previously by our team have demonstrated the fact that bloodletting puncture at hand twelve Jing-well points (HTWP) could alleviate cerebral edema, which mainly results from the disruption of blood-brain barrier (BBB). The study, therefore, was first designed to demonstrate whether BBB-protection serves an important role in the edema-relief effect of HTWP bloodletting, based on which to research the molecular mechanism underlying. METHODS: The rats were made into model suffering from permanent middle cerebral artery occlusion (pMCAO) and then bloodletting puncture were treated at HTWP once a day. Wet and dry weight method was adopted to evaluate the degree of brain edema, evans blue extravasation and electron microscopy were used to evaluate the integrity of the BBB, and RT-qPCR was carried out to analyze the expression level of occludin, claudin-5, ICAM-1, and VEGF. RESULTS: Results revealed that bloodletting puncture treatment could reduce water content of brain and the permeability of BBB caused by ischemic stroke. In bloodletting puncture group, ameliorated tight junctions could be observed under electron microscopy. It was demonstrated in further study that, in bloodletting group, compared with pMCAO one, the expression levels of occludin and claudin-5 were up-regulated, while ICAM-1 and VEGF were down-regulated. CONCLUSIONS: In conclusion, bloodletting puncture at HTWP might play a significant role in protecting the tight junctions of BBB, thus alleviating cerebral edema induced by ischemic stroke. Therefore, the therapy of bloodletting puncture at HTWP may be a promising strategy for acute ischemic stroke in the future.

The Need to Develop a Regulatory Body for the Practice of Al-Hijama.

Al-Hijama is a traditional therapy which has been extensively used in the Middle East. It has an Islamic basis but is used in many cultures in the form of wet cupping. There has been a significant growth in its availability in most Western countries during the last decade. In none is it subject to statutory regulation and the training and quality of practitioners is variable. It has both a preventive and therapeutic element and so there are appropriate concerns about the potential for incorrect diagnoses and delays in other effective treatments. In the past, the apprenticeship model in which a trainee worked for some years with an experienced ijazah ensured such problems did not arise. However, there is now an urgent need to recognise the widespread practice of this therapy and ensure that it has the benefits of statutory regulation, be this through specific regulatory bodies or a negative licensing model.

Effect of bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points on upper back myofascial pain syndrome: a randomized controlled trial.

OBJECTIVE: To observe the clinical efficacy of bloodletting therapy and acupuncture at Jiaji points for treating upper back myofascial pain syndrome (MPS), and compare this with lidocaine block therapy. METHODS: A total of 66 upper back MPS patients were randomly assigned to either the treatment group or the control group in a 1: 1 ratio. The treatment group (n = 33) were treated with bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points; one treatment course consisted of five, single 20-min-treatments with a 2-day break between each treatment. The control group (n = 33) were treated with a lidocaine block at trigger points; one treatment course consisted of five sessions of lidocaine block therapy with a 2-day break between each session. The simplified McGill Scale (SF-MPQ) and tenderness threshold determination were used to assess pain before and after a course of treatment. RESULTS: After the third and fifth treatment, the SF-MPQ values were significantly decreased (P < 0.01) and the tenderness thresholds were significantly increased (P < 0.01) in both groups compared with before treatment. There were no significant differences in pain assessments between the two groups after three and five treatments (P > 0.05). There were five cases with minor adverse reactions reported in the control patients, while no adverse reactions were reported in the treatment group. CONCLUSION: Bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji points was effective in treating upper back MPS. Clinically, bloodletting and acupuncture therapy had the same efficacy as the lidocaine block therapy, with fewer adverse reactions.

Bloodletting at Jing-well points decreases interstitial fluid flow in the thalamus of rats.

OBJECTIVE: To investigate the changes in the neuronal microenvironment of the middle cerebral artery (MCA) territory induced by Jing-well points bloodletting acupuncture (WPBA) and to explore the neuroprotective mechanism of WPBA in stroke. METHODS: Adult male Sprague Dawley (n = 32) rats were randomly divided into four groups of eight animals each: WPBA-thalamus group (WT), WPBA-caudate nucleus group (WC), sham-control thalamus group (ST) and sham-control caudate nucleus group (SC). Animals in the WT and WC groups received 2 µL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats' digits were used for WPBA. Although 2 µL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups (ST and SC), no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic resonance imaging. RESULTS: The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats' clearance rate, (7.47 ± 3.15) x 10(-5)/s (P.= 0.009); half-life, (1.52 ± 0.13) h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA (P = 0.649). In addition, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated between the WT and WC groups (P = 0.631, P = 0.970, respectively). CONCLUSION: The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.

Hijama improves overall quality of life in chronic renal failure patients: A pilot study.

Present study assesses the therapeutic effectiveness of Hijama (blood letting) inpatients of chronic renal failure undergoing hemodialysis for past several years with almost no urinary output.24 patients from Sindh Government Qatar Hospital Karachi were selected randomly under going dialysis 2-3 times/week for an average of 3 years under supervision of Dr. Khurram Danial, in-charge nephrologist at dialysis Centre Sindh Government Qatar Hospital Karachi after the written consent from patients. Each patient was subjected to Hijama session once a week after dialysis for a period of one year in a nearby hospital Aligarh Shifa with the consent of the ethical committee of the hospital. Serum urea, creatinine, complete blood count and electrolytes were determined prior to Hijama as baseline values and were again recorded on monthly basis for twelve months of Hijama sessions. The patient's feedback regarding quality of life after each Hijama session shows that almost all the patients reported a significant recovery from severe fatigue which they used to face during the interval between the dialysis sessions. There was significant recovery in all patients from anorexia and insomnia with the improvement in quality of life as compared to patients not undergoing Hijama. Both systolic and diastolic blood pressures were shifted towards normal in almost all patients after Hijama. Serum Creatinine level was declined significantly, while electrolyte and hematological parameters were also improved significantly. The hemoglobin of all patients undergoing Hijama was maintained near normal without any blood transfusion, which was frequently needed in patients not undergoing Hijama sessions. There was insignificant improvement in Urinary output in 2 out of 24 patients. Results of the present study suggest that Hijama may be performed safely in patients of chronic renal failure on dialysis with overall improvement in quality of life, since there was reduction in fatigue, improvement in appetite, quality of sleep and platelet count.

Brain susceptibility weighted imaging signal changes in acute hemorrhagic anemia: an experimental study using a rabbit model.

BACKGROUND: The aim of this study was to investigate susceptibility-weighted imaging (SWI) signal changes in different brain regions in a rabbit model of acute hemorrhagic anemia. MATERIAL/METHODS: Ten New Zealand white rabbits were used for construction of the model of acute hemorrhagic anemia. Signal intensities of SWI images of the bilateral frontal cortex, frontal white matter, temporal lobe, and thalamic nuclei were measured. In addition, the cerebral gray-white contrast and venous structures of the SWI images were evaluated by an experienced physician. RESULTS: Repeated bloodletting was associated with significant reductions in red blood cell count, hemoglobin concentration, hematocrit, pH, and PaCO2, and elevations of blood lactate and PaO2. In normal status, the SWI signal intensity was significantly higher in the frontal cortex than in the frontal white matter (63.10±22.82 vs. 52.50±20.29; P<0.05). Repeated bloodletting (5 occasions) caused significant (P<0.05) decreases in the SWI signals of the frontal cortex (from 63.10±22.82 to 37.70±4.32), temporal lobe (from 52.50±20.29 to 42.60±5.54), and thalamus (from 60.40±20.29 to 39.40±3.47), but was without effect in the frontal white matter. The cerebral white-gray contrast and venous structures were clearer after bloodletting than before bloodletting. CONCLUSIONS: The effect of hemorrhage on the brain is reflected by SWI signal changes in the cerebral cortex and gray matter nuclei.